Differential effects of γ-state-triggered thalamic stimulation on mechanical sensitivity in neuropathic rats

To develop and evaluate a thalamic γ-state-triggered closed-loop (CL) deep brain stimulation (DBS) strategy for modulation of neuropathic pain.

Neuropathic pain was induced with chronic constriction injury (CCI) in rats. Thalamic local field potentials (LFPs) were used to identify wavelet-packet (WP)-defined gamma (γ)-band states, γ⁰ and γ¹, using coefficient magnitudes relative to an adaptive threshold and temporal confirmation. A CL DBS paradigm triggered stimulation contingent on either γ⁰ or γ¹ states and was compared with conventional open-loop (OL) 40 Hz and 130 Hz stimulation using behavioral and neurophysiological outcomes.

CCI increased thalamic γ power on days 3, 7 and 14 (raw p = 0.0004, 0.0078 and 0.0162; FDR-adjusted p = 0.0077, 0.0703 and 0.0731) and prolonged γ¹-state duration (raw p = 0.0283; adjusted p = 0.1417). In the CCI model, γ power was negatively associated with mechanical withdrawal threshold (MWT; raw p = 0.0159; adjusted p = 0.0956). At 130 Hz, mean MWT changes were opposite under the two CL protocols: γ⁰ CL increased MWT by 47.07% and γ¹ CL decreased it by 12.06% (raw p = 0.0234 and 0.0391; adjusted p = 0.0469 and 0.0586). The 40 Hz γ⁰ CL protocol produced the largest observed mean MWT increase of 81.91% (raw p = 0.0078; adjusted p = 0.0469), 46.02 percentage points above 40 Hz OL. Electrophysiological analyses also showed protocol-associated changes in γ-state dynamics and nominal spectral-power changes.

The tested WP-defined γ-state-triggered CL protocols were associated with differing changes in mechanical sensitivity in neuropathic rats. These findings support further evaluation of this approach as a candidate framework for adaptive neuromodulation of neuropathic pain.